Abstract:

Background: Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP), commonly substitutes sugar, and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice.

Objective: We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE’s inhibition of endogenous IAP.

Design: In vitro model: IAP was added to diet and regular soda, and IAP activity was measured. Acute model: A closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. Chronic model: Mice were fed chow or high fat diet (HFD) with/without ASP in the drinking water for 18 weeks.

Results: In vitro study: IAP activity was lower (p<.05) in solutions containing ASP compared to controls. Acute model: endogenous IAP activity was reduced by 50% in the ASP group compared to controls (0.2±0.03 vs 0.4±0.24) (p=.02). Chronic model: Mice in the HFD+ASP group gained more weight compared to HFD+water group (48.1±1.6 vs 42.4±3.1, p=.0001). Significant difference in glucose intolerance between HFD +/- ASP groups (53913±4000.58mg*min/dL vs 42003.75±5331.61mg*min/dL, respectively, p=.02). Fasting glucose and serum TNF-alpha levels were significantly higher in the HFD+ASP group (1.23 and 0.87 fold increases, respectively, p=.006 and p=.01).

Conclusions: Endogenous IAP’s protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of aspartame, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks.

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